Hirofumi Yurie

The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model

Background Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit. Methods We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery. Results Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01). Conclusions We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.

Plasma micrornas Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats

Background The development of effective immunosuppressive regimens has resulted in many cases of successful hand transplantation. Visual skin inspection and histological evaluation are used to assess the rejection of hand transplants, but these methods are largely subjective. In this study, we aimed to determine the potential of microRNAs (miRNAs) as biomarkers for acute rejection in vascularized composite allotransplants. Methods In allograft group, 7 male Brown-Norway rats (RT1n) were used as donors and 13 male Lewis rats (RT1l) were used as recipients. In control group, 8 Lewis rats were used as donors and recipients. The hindlimbs of donor rats were transplanted orthotopically to recipient rats. Skin changes were noted daily. Skin biopsies were obtained from 5 recipients and evaluated histologically. Plasma samples were obtained from the other 8 recipients before transplant and 7, 10, and 14 days posttransplant and used to measure miRNA expression. Results Skin changes occurred at a mean of 11.0 days posttransplant. Rejection in most skin biopsies taken 7 and 10 days posttransplant was histologically classified as grade 0, whereas that in most biopsies taken 14 days posttransplant was classified as grade 3. We found that expression of miRNA-146a and miRNA-155 was significantly upregulated at 10 and 14 days posttransplant compared with that at 7 days posttransplant. In control group, there were no significant changes in plasma miRNAs expressions. Conclusions The upregulation of plasma miRNA-146a and miRNA-155 was detected before the histological evaluation methods could diagnose complete rejection in the rat hindlimb transplantation model. Plasma miRNA-146a and miRNA-155 may be potential biomarkers of acute rejection after vascularized composite allotransplantation.

Recipient bone marrow-derived stromal cells prolong graft survival in a rat hind limb allotransplantation model

Recent studies have indicated that bone marrow‐derived stromal cells (BMSCs) have immunomodulatory properties that suppress the T cell responses that cause graft rejection. The purpose of this study is to evaluate the effect of recipient BMSCs intravenous infusion for immunomodulation in a rat vascularized composite allotransplantation model.

A nerve conduit containing a vascular bundle and implanted with bone marrow stromal cells and decellularized allogenic nerve matrix.

Cells, scaffolds, growth factors, and vascularity are essential for nerve regeneration. Previously, we reported that the insertion of a vascular bundle and the implantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into a nerve conduit promoted peripheral nerve regeneration. In this study, the efficacy of nerve conduits containing a vascular bundle, BM-MSCs, and thermally decellularized allogenic nerve matrix (DANM) was investigated using a rat sciatic nerve model with a 20-mm defect. Lewis rats were used as the sciatic nerve model and for the preparation of BM-MSCs, and Dark Agouti rats were used for the preparation of the DANM. The revascularization and the immunogenicity of the DANM were investigated histologically. The regeneration of nerves through nerve conduits containing vessels, BM-MSCs, and DANM (VBD group) was evaluated based on electrophysiological, morphometric, and reinnervated muscle weight measurements and compared with that of vessel-containing conduits that were implanted with BM-MSCs (VB group). The DANM that was implanted into vessel-containing tubes (VCTs) was revascularized by neovascular vessels that originated from the inserted vascular bundle 5–7 days after surgery. The number of CD8+ cells found in the DANM in the VCT was significantly smaller than that detected in the untreated allogenic nerve segment. The regenerated nerve in the VBD group was significantly superior to that in the VB group with regard to the amplitude of the compound muscle action potential detected in the pedal adductor muscle; the number, diameter, and myelin thickness of the myelinated axons; and the tibialis anterior muscle weight at 12 and 24 weeks. The additional implantation of the DANM into the BM-MSC-implanted VCT optimized the axonal regeneration through the conduit. Nerve conduits constructed with vascularity, cells, and scaffolds could be an effective strategy for the treatment of peripheral nerve injuries with significant segmental defects.

Opening Wedge Osteotomy for Valgus Deformity of the Little Finger after Proximal Phalangeal Fracture in Children: Two Case Reports

In the treatment of posttraumatic valgus deformity of the pediatric little finger, it is usually difficult to achieve accurate correction of angular and rotational deformity using closing wedge osteotomy. We report two cases of valgus deformity of the little finger (both 11-year-old female patients) successfully treated using opening wedge osteotomy followed by intramedullary semirigid fixation with a single Kirschner wire. A wire tip inserted from the retrocondylar fossa of the proximal phalangeal head was advanced along the radial side of the intramedullary cortex after gradual opening of the osteotomy site. If needed, further fine adjustment of the rotational alignment can be performed even after K-wire insertion. Postoperatively, the gap between the little and ring fingers in the fully extended and adducted position and the finger overlapping in the fully flexed position were completely resolved. The flexibility of the pediatric bone and sagittal clearance between the wire and the inner wall of the proximal phalangeal medullary cavity allow fine adjustment of the rotational alignment even after wire insertion.

MicroRNAs are potential objective and early biomarkers for acute rejection of transplanted limbs in a rat model

Limb transplantation is considered to be a treatment option for amputees. Visual skin inspection and histological assessment are used to assess rejection, but these techniques are largely subjective. Using a rat model, we examined the potential of several microRNAs (miRNAs) to be used as objective and minimally invasive biomarkers of acute rejection of transplanted limbs.

Percutaneous Fixation for Scaphoid Nonunion with Bone Grafting Through the Distal Insertion Hole of a Fully Threaded Headless Screw.

BACKGROUND Percutaneous scaphoid screw fixation is a popular treatment for acute scaphoid fractures with no or minimal displacement. For treating scaphoid nonunions, however, open reduction and internal fixation with bone grafting is still the most popular treatment. Percutaneous fixation with bone grafting through the screw insertion hole has received little attention, although it minimizes damage to the surrounding tissues. We report excellent results of six scaphoid nonunions treated by retrograde percutaneous fixation with curettage and bone grafting through the distal insertion hole of a fully threaded headless screw. METHODS Six scaphoid nonunions with substantial bone loss were treated, including one revision case. All nonunions were located at the middle third of the scaphoid. The mean patient age at operation was 26 years, and the mean interval between fracture and surgery was 7 months. In the revision case, the interval between the primary and revision surgery was 6 months. In one case, curettage alone was performed before retrograde insertion of the headless screw. In the other cases including the revision, curettage and bone grafting with a bone biopsy needle was required through a distal insertion hole. RESULTS The mean follow-up was 11.3 months. Radiologically, union was achieved at averaged 12 weeks postoperatively. At the final follow-up, there was significant improvement in the wrist extension range of movement (from 65.8° to 80.8°) and grip strength (from 69.5% to 93.0% of the unaffected side). Five patients were free of pain, and one experienced mild pain only during heavy manual labor. The mean VAS, DASH, and Cooney wrist scores were 0.3, 1 and 99, respectively. All patients returned to their work or athletic activities. CONCLUSIONS Retrograde percutaneous fixation with bone grafting through the distal insertion hole of a fully threaded headless screw is a promising option for surgical treatment of scaphoid nonunions.

Percutaneous Fixation for Scaphoid Nonunion With Bone Grafting Through the Distal Insertion Hole of a Fully Threaded Headless Screw

Objective: Percutaneous scaphoid screw fixation is a popular treatment for acute scaphoid fractures with no or minimal displacement. For treating scaphoid nonunions, however, open reduction and internal fixation with bone grafting is still the most popular treatment. Percutaneous fixation with bone grafting through the screw insertion hole has received little attention, although it minimizes damage to the surrounding tissues. We report excellent results of 10 scaphoid nonunions treated by retrograde percutaneous fixation with curettage and bone grafting through the distal insertion hole of a fully threaded headless screw. Materials and Methods: Ten scaphoid nonunions with substantial bone loss were treated, including 1 revision case. All nonunions were located at the middle third of the scaphoid. The mean patient age at operation was 24.7 years, and the mean interval between fracture and surgery was 8.8 months. In the revision case, the interval between the primary and revision surgery was 6 months. Surgery was performed under general anesthesia or an axillary brachial plexus block with local anesthesia at the iliac crest donor site. A 1.1-mm guidewire was percutaneously inserted into the scaphoid tuberosity and advanced to the proximal pole of the scaphoid with the wrist in an extended and ulnar-deviated position. A 1.2-mm second derotation wire was also inserted radial or ulnar to the original guidewire. A 2.0-mm cannulated drill was passed over the guidewire, stopping at the distal end of the cystic lesion. The guidewire was then removed. The 1.2-mm second derotation wire maintained the reduction of the scaphoid. Curettage inside the cystic lesion was performed using a small curette inserted through the distal insertion hole. Bone graft was harvested percutaneously from the iliac crest with an 11-gauge bone biopsy needle and inserted into the cystic lesion through the drill hole of the distal scaphoid fragment. The removed guidewire was reinserted into the previously drilled hole followed by insertion of a selected fully threaded headless screw (Acutrak 2 mini; Acumed, Hillsboro, OR, USA). After the operation, the wrist was immobilized in a thumb spica cast for the initial 6 weeks, followed by splinting until bone union was confirmed. In one case, curettage alone was performed before retrograde insertion of the headless screw. In the other cases including the revision, curettage and bone grafting with a bone biopsy needle was required through a distal insertion hole. Results: The mean follow-up was 12.1 months. Radiologically, union was achieved at averaged 12 weeks postoperatively. At the final follow-up, there was significant improvement in the wrist extension range of movement (from 65.8° to 80.8°) and grip strength (from 65.5% to 87.8% of the unaffected side). Nine patients were free of pain, and 1 experienced mild pain only during heavy manual labor. The mean visual analogue scale (VAS), Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), and Cooney wrist scores were 0.1, 1.75, and 98.5, respectively. All patients returned to their work or athletic activities. Conclusions: Retrograde percutaneous fixation with bone grafting through the distal insertion hole of a fully threaded headless screw is a promising option for surgical treatment of scaphoid nonunions.